Vaccine compositions often include immunological adjuvants to enhance immune responses. For example, Complete Freund's adjuvant (CFA) is a powerful immunostimulatory agent that has been successfully used with many antigens on an experimental basis. CFA includes three components: a mineral oil, an emulsifying agent, and killed mycobacteria, such as Mycobacterium tuberculosis. Aqueous antigen solutions are mixed with these components to create a water-in-oil emulsion. Although effective as an adjuvant, CFA causes severe side-effects, including pain, abscess formation and fever, primarily due to the presence of the mycobacterial component. CFA, therefore, is not used in human and veterinary vaccines.
Immunologic adjuvants help increase immune responses induced by vaccines. Different mechanisms have been proposed to explain the enhanced antigen specific immune response generated by adjuvanted vaccine. First, adjuvant can promote a slow release of the antigen exposing it to the immune system for a longer period of time and consequently stimulating a stronger and possibly better defined immune response. Second, adjuvant can also help delivery and uptake of the antigenic complex to antigen presenting cells (APCs) such as macrophages and dendritic cells which in turn can migrate to lymphoid organs and initiate a concerted response in interaction with T and B cells. Third, immune cells including APCs can be directly activated by adjuvant and then initiate a faster and stronger immune response through the subsequent stimulation of T and B cells. Oil-in-water emulsion ingested by macrophage which then can migrate to draining lymph nodes, or TLRs stimulating molecules such as unmethylated CpG dinucleotide-containing DNA, are examples of adjuvant acting mainly according to these mechanisms. An interesting paradigm regarding immune reaction is that immune responses are generally more robust when stimulated by an antigen of rare occurrence than by an antigen frequently encountered in nature. The present study explores the possibility of using short peptidic sequences not present or observed only once in known proteomes as immunomodulators to enhance vaccine-induced immune responses and protection against lethal viral infections.